Method of preparing N-phosphonomethyl glycine

ABSTRACT

To prepare N-phosphonomethyl glycine, 
     a) aminomethylphosphonic acid or one of its salts in water, if necessary or desirable with the addition of lyes, is reacted with an alkali carbonate and/or alkali hydrogencarbonate or with carbon dioxide and a lye, 
     b) the resulting alkali salt of N-phosphonomethylcarbamic acid is subsequently hydroxymethylated with formaldehyde, 
     c) the salts, resulting from b), of N-hydroxymethyl-N-phosphonomethyl-carbamic acid, if necessary or desirable with addition of a lye, are reacted with hydrocyanic acid and/or a cyanide and 
     d) the N-carboxy-N-phosphonomethylglyconitrile salts thus obtained are treated with acids and converted by means of hydrolysis and decarboxylation into N-phosphonomethyl glycine. 
     In this way, it is possible to obtain excellent yields of high-purity N-phosphonomethyl glycine.

This application is the national phase of PCT/EP97/03955 filed Feb. 22,1997.

The subject matter of the invention is a method of preparingN-phosphonomethyl glycine from aminomethylphosphonic acid or one of itssalts.

N-phosphonomethyl glycine (glyphosate) has been in use for more than 20years as a systemic herbicide, the action of which is based oninhibition of the plant enzyme 5-enolpyruvylshikimat-3-phosphatesynthetase (EPSP synthetase) and thus of aromatic amino acid synthesis.

Of the many syntheses which have been developed for N-phosphonomethylglycine, technical significance has been attached, amongst otherreactions, to reactions in which an amino component is hydroxymethylatedor cyanomethylated by reacting it with formaldehyde or with formaldehydeand hydrocyanic acid respectively.

A familiar disadvantage of the hydroxymethylation and cyanomethylationof primary amines is that one usually obtains mixtures of mono- anddi-substituted products.

According to the Polish patent PL 156 933, for example, in whichaminomethylphosphonic acid is reacted with formalin and sodium cyanideat a pH of 10, and the initially formed nitriles are subsequentlyhydrolysed, one obtains not only the main product N-phosphonomethylglycine, but also the by-product N-phosphonomethyliminodiacetic acid.U.S. Pat. No. 4,221,583 describes the reaction of aminomethylphosphonicacid with formaldehyde and sodium cyanide at pH levels of 6.6 to 9.7; inthis case, the yield of N-phosphonomethylglyconitrile is only 65%.

During hydroxymethylation and analogous reactions of primary amines itshould be possible to prevent the formation of di-substituted productsby introducing a protective group temporarily into the amine. Asynthesis of this kind, in which N-phosphonomethyl glycine is obtainedfrom glycine, is disclosed in European patent 112 580. When glycine isreacted with sodium carbonate, it is first converted into the sodiumsalt of the corresponding carbamic acid. Subsequent reaction withformalin and diethyl phosphite leads to formation ofN-carboxy-N-(O,O'-diethylphosphonomethyl)glyconitrile, from whichN-phosphonomethyl glycine is obtained by way of hydrolysis. However, the36% yield from this method is also extremely low.

The object of the invention is thus to provide a technicallyuncomplicated method of preparing N-phosphonomethyl glycine, which doesnot have the disadvantages of the prior art and with which high yieldsof high-purity compound are obtained.

This object is established according to the invention in that

a) aminomethylphosphonic acid or one of its salts in water, if necessaryor desirable with the addition of lyes, is reacted with an alkalicarbonate and/or alkali hydrogencarbonate or with carbon dioxide and alye,

b) the resulting alkali salt of N-phosphonomethylcarbamic acid ishydroxymethylated with formaldehyde,

c) the salts, resulting from b), ofN-hydroxymethyl-N-phosphonomethylcarbamic acid, if necessary ordesirable with addition of a lye, are reacted with hydrocyanic acidand/or a cyanide and

d) the N-carboxy-N-phosphonomethylglyconitrile salts thus obtained aretreated with acids and converted by means of hydrolysis anddecarboxylation into N-phosphonomethyl glycine.

Surprisingly, one obtains an excellent yield of high-purityN-phosphonomethyl glycine in this way, with relatively uncomplicatedtechnical equipment. What is especially surprising is that during thereaction only very small proportions (<0.5%) ofN-phosphonoethyliminodiacetic acid are formed, and none is contained inthe isolated N-phosphonomethyl glycine.

According to the invention, N-phosphonomethyl glycine is prepared fromaminomethylphosphonic acid in a number of steps; however, as per aspecial embodiment, the intermediates need not be isolated and theentire process can be carried out as a one-pot reaction.

In the first step a), aminomethylphosphonic acid or one of its salts inwater--if necessary or desirable with the addition of lyes--is reactedwith an alkali carbonate and/or alkali hydrogencarbonate, or with carbondioxide and a lye; the amino group is carboxylated, and salts ofN-phosphonomethylcarbamic acid are formed, having the formula (I):##STR1##

Since the reaction ensues in water, it is preferable to use awater-soluble alkali carbonate and/or alkali hydrogencarbonate.Particular preference is given to sodium and potassium salts, some ofwhich can also be used in the form of their hydrates. As lye, use ismade preferably of sodium or potassium hydroxide solution. Instead ofmaking direct use of alkali carbonate and/or alkali hydrogencarbonate,it is also possible to react the aminomethylphosphonic acid in waterwith carbon dioxide and a lye.

It is an essential feature of the invention that reaction step a) becarried out in water. The pH can be varied within wide limits and assumevalues preferably between 7 and 14; it is more preferable still if thepH is between 9 and 11. Where use is made of alkali carbonates and/oralkali hydrogencarbonates, the pH can be adjusted to a higher value ifso desired by addition of lye.

The molar ratio of aminomethylphosphonic acid or one of its salts toalkali carbonate or alkali hydrogencarbonate can also be varied withinwide limits. A molar ratio of 0.9 to 1.2 is preferred. The easiest wayto adjust the pH to the desired value is to add suitable quantities of alye either before or during the reaction.

For reaction step a) the temperature is not critical. It is preferablybetween 0 and 80° C. Too high a temperature, however, should be avoidedin order to prevent decarboxylation of the carbamic acid or its salts.An especially preferred embodiment provides for a reaction temperatureof 10 to 30° C.

The concentration of the reaction mixture in step a) is also largelyunproblematic. A concentration range from 10 to 30 wt. %, calculated interms of the aminomethylphosphonic acid or the corresponding salt, isrecommended.

In reaction step b), the N-phosphonomethylcarbamic acid salt formedduring step a) is reacted, preferably without prior isolation, withformaldehyde to form a salt--with the formula (II)--ofN-hydroxymethyl-N-phosphonomethylcarbamic acid. ##STR2##

Insofar as is necessary, the pH is adjusted to a level in the range from7 to 14, preferably 9 to 11, by simultaneous addition of lye. To thisend, sodium or potassium hydroxide solution are used to good effect.

The formaldehyde can be used in the form of an aqueous solution(formalin) or in the form of paraformaldehyde. The molar ratio offormaldehyde to the aminomethylphosphonic acid used in step a) ispreferably between 0.9 and 1.2.

For reaction step b), the temperature is again not critical, preferablybeing between 0 and 80° C. Too high a temperature, however, should beavoided in order to prevent decarboxylation ofN-hydroxymethyl-N-phosphonomethylcarbamic acid or its salts. Accordingto an especially preferred embodiment, therefore, the reactiontemperature is adjusted to within the range from 10 to 30° C.

In reaction step c), the N-hydroxymethyl-N-phosphonomethylcarbamic acidsalt formed during step b) is reacted--preferably without priorisolation--in aqueous alkaline solution with hydrocyanic acid or acyanide to form a salt of N-carboxy-N-phosphonomethylglyconitrile withthe formula (III). ##STR3##

Where use is made of cyanides, the water-soluble alkali cyanides, suchas sodium and potassium cyanide, are preferred. The molar ratio ofhydrocyanic acid or cyanide to the aminomethylphosphonic acid used instep a) is preferably in the range from 0.9 to 1.5.

For carrying out step c), it is of advantage to select the reactiontemperature and the pH such that they correspond to the conditions underwhich step b) is conducted. This avoids the possible need fortime-consuming reaction-control modifications. If necessary ordesirable, the pH can be kept constant by simultaneous metering of alye--preferably sodium or potassium hydroxide solution.

In reaction step d) of the method of the invention, theN-carboxy-N-phosphono-methylglyconitrile salt formed in step c) istreated with acids. Following decarboxylation and hydrolysis of thenitrile group, the desired N-phosphonomethyl glycine (IV) is formed.##STR4##

The acids used are preferably common inorganic or organic acids, eg,hydrochloric, sulfuric, nitric and phosphoric acids, or formic andacetic acids. According to a preferred embodiment, use is made ofconcentrated aqueous hydrochloric acid in a molar ratio of about 4 to 8to the aminomethylphosphonic acid used in step a).

Reaction step d) is preferably carried out at a temperature of 80 to120° C. in order to ensure a high reaction rate.

N-phosphonomethyl glycine can be isolated using familiar methods fromthe reaction mixture obtained from step d). The following twotechniques, however, are preferred:

First of all, the reaction mixture is freed of the aqueous hydrochloricacid by means of familiar methods; the residue is taken up in hot waterand the pH adjusted with bases, especially sodium hydroxide solution, to1.5 to 3.0. When the solution is cooled, the desired reaction productprecipitates in the form of a fine crystalline powder. This may bewashed, if necessary, with water and dried under vacuum.

Alternatively, following removal of excess salts, methanol can be addedto the solution of N-phosphonomethyl glycine in hot water; as themixture cools, the product crystallizes out as a fine powder.

With the method of the invention, which comprises several reaction stepsbut which, as already described, can be carried out as a one-potreaction, and which is relatively easy to implement for industrial-scaleproduction, one obtains yields of N-phosphonomethyl glycine of up to 88%of the theoretical yield (calculated in terms of aminomethylphosphonicacid) and a purity level of about 97 to 98%.

The following examples serve to explain the invention in more detail.

EXAMPLE 1

11.1 g (0.1 mol) aminomethylphosphonic acid are suspended in 35 g waterand the pH is adjusted to 2.6 by addition of 25% sodium hydroxidesolution. At a temperature of 20° C., 28.9 g (0.1 mol) sodium carbonatedecahydrate are added. On completion of the addition, the pH of thesolution is adjusted to 10 with 25% sodium hydroxide solution. Within aperiod of 38 minutes and at a temperature of about 20° C., 11.0 g of a30% formalin solution are added to the reaction solution, together with25% sodium hydroxide solution (pH 10). On completion of the addition,altogether 20 g (0.12 mol) of 25% sodium hydroxide solution have beenconsumed. Over a period of 11 minutes, 2.97 g (0.11 mol) hydrocyanicacid are added dropwise to the 20° C. solution, which is then left tostand for 2 h at room temperature. The pH remains at 10 during and afterthe addition of hydrocyanic acid.

To effect hydrolysis, the reaction mixture is blended carefully with 79g (0.8 mol) of 37% aqueous hydrochloric acid. When no more gas isgenerated, the mixture is refluxed for 6 h before being boiled todryness. The residue is digested in 68 g of 37% hydrochloric acid andthe mixture then filtered. The filtrate is boiled down, and theresulting residue taken up in about 60 ml of boiling water. The clearsolution is added to 60 ml methanol and the mixture cooled to about 5°C., whereupon the product crystallizes out as a fine powder. This isseparated off by filtration, washed free of chloride with some 58 gwater, and then dried at about 50° C. under vacuum.

One obtains 12.8 g N-phosphonomethyl glycine (77.5% of the theoreticalyield calculated in terms of aminomethylphosphonic acid), with atritrimetrically determined content of 97.7%. Ion chromatography showsthe combined aqueous filtrates still to have a 10.5% content ofN-phosphonomethyl glycine, which can be isolated in the usual way.

EXAMPLE 2

1.1 g (0.1 mol) aminomethylphosphonic acid are suspended in 35 g waterand the pH is adjusted to 2.6 by addition of 25% sodium hydroxidesolution. At a temperature of 20° C., 28.9 g (0.1 mol) sodium carbonatedecahydrate are added. On completion of the addition, the pH of thesolution is adjusted to 10 with 25% sodium hydroxide solution. Within aperiod of 40 minutes and at a temperature of about 21° C., 3.3 g (0.11mol) paraformaldehyde are added to the reaction solution, together with25% sodium hydroxide solution (pH 10). On completion of the addition,altogether 18.2 g (0.11 mol) of 25% sodium hydroxide solution have beenconsumed. Over a period of 11 minutes, 2.97 g (0.11 mol) hydrocyanicacid are added dropwise to the 21° C. solution, which is then left tostand for 1 h at room temperature. The pH remains at 10 during and afterthe addition of hydrocyanic acid.

To effect hydrolysis, the reaction mixture is blended carefully with 79g (0.8 mol) of 37% aqueous hydrochloric acid. When no more gas isgenerated, the mixture is refluxed for 6 h before being boiled todryness. The residue is digested in 68 g of 37% hydrochloric acid andthe mixture then filtered. The filtrate is boiled down, and theresulting residue taken up in about 65 ml of boiling water. The clearsolution is added to 65 ml methanol and the mixture cooled to about 5°C., whereupon the product crystallizes out as a fine powder. This isseparated off by filtration, washed free of chloride with some 72 gwater, and then dried at about 50° C. under vacuum.

One obtains 12.7 g N-phosphonomethyl glycine (77.7% of the theoreticalyield calculated in terms of aminomethylphosphonic acid), with atritrimetrically determined content of 97.3%. Ion chromatography showsthe combined aqueous filtrates still to have an 8.7% content ofN-phosphonomethyl glycine, which can be isolated in the usual way.

EXAMPLE 3

11.1 g (0.1 mol) aminomethylphosphonic acid are suspended in 35 g water.At a temperature of 20° C., 28.9 g (0.1 mol) sodium carbonatedecahydrate are added.

On completion of the addition, the pH of the solution is adjusted to 10with 25% sodium hydroxide solution. Within a period of 35 minutes and ata temperature of about 22° C., 3.3 g (0.11 mol) paraformaldehyde areadded to the reaction solution, together with 25% sodium hydroxidesolution. On completion of the addition, altogether 15.9 g (0.1 mol) of25% sodium hydroxide solution have been consumed. Over a period of 10minutes, 2.97 g (0.11 mol) hydrocyanic acid are added dropwise to the22° C. solution, which is then left to stand for 2 h at roomtemperature. The pH remains at 10 during and after the addition ofhydrocyanic acid.

To effect hydrolysis, the reaction mixture is blended carefully with 79g (0.8 mol) of 37% aqueous hydrochloric acid. When no more gas isgenerated, the mixture is refluxed for 6 h before being boiled todryness. The residue is taken up in about 70 g of boiling water, and thepH adjusted to 2 with 50% sodium hydroxide solution. When the mixture iscooled, the product crystallizes out as a fine powder. This is separatedoff by filtration, washed free of chloride with some 75 g water, andthen dried at about 50° C. under vacuum.

One obtains 10.7 g N-phosphonomethyl glycine (63.9% of the theoreticalyield calculated in terms of aminomethylphosphonic acid), with atritrimetrically determined content of 95.8%. Ion chromatography showsthe combined aqueous filtrates still to have a 24% content ofN-phosphonomethyl glycine. The solution does not contain anyN-phosphonomethyliminodiacetic acid.

What is claimed is:
 1. A method of preparing N-phosphonomethyl glycine,comprisinga) reacting aminomethylphosphonic acid or one of its salts inwater, with an alkali carbonate, an alkali hydrogencarbonate,or withcarbon dioxide and a lye, b) hydroxy-methylating the resulting alkalisalt of N-phosphonomethyl carbamic acid with formaldehyde to form saltsof N-hydroxymethyl-N-phosphonomethyl-carbamic acid; c) reacting saidsalts of N-hydroxymethyl-N-phosphonomethyl-carbamic acid, withhydrocyanic acid or a cyanide and d) treating the resultantN-carboxy-N-phosphonomethylglyconitrile salts with acids and convertingby means of hydrolysis and decarboxylation into N-phosphonomethylglycine.
 2. The method of claim 1, wherein sodium or potassium hydroxidesolution is used as lye.
 3. The method of claim 1, wherein the alkalicarbonate or alkali hydrogencarbonate is a water-soluble sodium orpotassium compounds.
 4. The method of claim 1, wherein step a) iscarried out in aqueous solution at a pH of 7 to
 14. 5. The method ofclaim 1, wherein use is made of 0.9 to 1.2 mol alkali carbonate oralkali hydrogencarbonate, or of CO₂, per mol of aminomethylphosphonicacid (salt).
 6. The method of claim 1, wherein step a) is carried out ata temperature from 0 to 80° C.
 7. The method of claim 1, wherein theconcentration of the aqueous alkaline solution in step a) is adjusted to10 to 30 wt. %, calculated in terms of the aminomethylphosphonic acid orsalt thereof.
 8. The method of claim 1 wherein for step b), use is madeof 0.9 to 1.2 mol formaldehyde per mol of amino-methylphosphonic acidused in step a).
 9. The method of claim 1, wherein step b) is carriedout at the same pH and in the same temperature range as step a).
 10. Themethod of claim 1, wherein for step c), hydrocyanic acid/or cyanide areused in an amount of 0.9 to 1.5 mol per mol of aminomethylphosphonicacid (salt).
 11. The method of claim 1, wherein step c) is carried outat the same pH and temperature as step b).
 12. The method of claim 1,wherein the hydrolysis is carried out in the presence of an inorganic ororganic acid.
 13. The method of claim 12, wherein concentratedhydrochloric acid is used as inorganic acid.
 14. The method of claim 1,wherein for the hydrolysis, the inorganic or organic acid is used in aquantity of 4 to 8 mol per mol of aminomethylphosphonic acid or saltthereof.
 15. The method of claim 1, wherein step d) is carried out at atemperature of 80 to 120° C.
 16. The method of claim 1, wherein stepsa), b), c) and d) are carried out in the form of a one-pot reaction. 17.The method of claim 1, wherein the N-phosphonomethyl glycine formed isisolated.